Effective manipulation of immune responses for the benefit of patients with cancer will require a better understanding of the type of immune response that is best able to control a particular tumor and procedures to manipulate the immune response favorably. The experiments proposed in this project will approach these goals through a coordinated study of several aspects of human and murine mammary cancer. Different types or manifestations of cell mediated immunity are measured with varying sensitivity by the assays in current use. Four assays of tumor specific cell mediated immunity (Cr51 release assay, microcytotoxicity assay, activated macrophage assay, and inhibition of DNA synthesis assay) will be used in this study. These assays were selected because they appeared to measure relevant but separate parameters of cell mediated immunity. They will not interfere with the care of patients. Antibody against tumor will be measured by several assays including the ability to block cell mediated immunity in the above assays. By comparing the results of these studies with histologic examination of the tumor and lymphoid tissue, with the clinical course of the tumor, and with the results of parallel studies with murine mammary cancer, it should be possible to define with greater precision the role of the various types of immune responses in the control of breast cancer. Methods for the preparation of chemically modified tumor cell antigens and synthetic adjuvants which selectively stimulate strong tumor specific cell mediated immunity are being developed in other experimental systems. Experiments with immunotherapy of autochthonous and transplanted murine mammary breast tumors will explore the potential of these methods for the treatment of human breast cancer.